Comparative Efficacy of Nutraceuticals and Conventional Medicines in Hypertension Treatment: A Critical Review of Current Evidence

Arnab Roy, Sajid Ansari, Faiz Alam , Chandan Kumar, Ayush Kumar, Alijan Mansur, Shahid Afridi, Md. Abu Alkama, Sarosh Alam , Mayank Prasad , Saurabh Choudhary, Aryan Raj , Udit Raj , Md. Kaif , Ataul Ansari , Kamlesh Kumar , Makhmur Hayat , Indrajeet Kumar Mahto ,

doi:10.5281/zenodo.16777401

Review Paper | Open Access
Volume 03 | Issue 08 | Article Id IJPS/250308033

Comparative Efficacy of Nutraceuticals and Conventional Medicines in Hypertension Treatment: A Critical Review of Current Evidence
Arnab Roy* Sajid Ansari Faiz Alam Chandan Kumar Ayush Kumar Alijan Mansur Shahid Afridi Md. Abu Alkama Sarosh Alam Mayank Prasad Saurabh Choudhary Aryan Raj Udit Raj Md. Kaif Ataul Ansari Kamlesh Kumar Makhmur Hayat Indrajeet Kumar Mahto
Department of Pharmacy, Faculty of Medical Science and Research, Sai Nath University, Ranchi, Jharkhand 835219, India.

Abstract

Hypertension affects over 1.13 billion people worldwide and remains a leading risk factor for cardiovascular disease, stroke, and kidney disease. While conventional antihypertensive medications have established efficacy, growing interest in nutraceuticals as complementary or alternative treatments has emerged due to their perceived safety profile and natural origin. This comprehensive review critically examines current evidence comparing the efficacy of nutraceuticals versus conventional medicines in hypertension management. We analyzed peer-reviewed studies published between 2018-2024, focusing on randomized controlled trials and meta-analyses. The evidence suggests that while conventional antihypertensive medications demonstrate superior and consistent blood pressure reduction, certain nutraceuticals show modest but statistically significant effects. Garlic extracts, hibiscus tea, beetroot juice, and omega-3 fatty acids demonstrate the strongest evidence among nutraceuticals, with systolic blood pressure reductions ranging from 3-8 mmHg. However, conventional medications achieve greater reductions (10-20 mmHg) with more predictable dose-response relationships. The review identifies gaps in long-term safety data for nutraceuticals and emphasizes the need for standardized dosing protocols. Integration of evidence-based nutraceuticals with conventional therapy may offer synergistic benefits, particularly in early-stage hypertension and as adjuvant therapy.

Keywords

Hypertension, nutraceuticals, antihypertensive drugs, blood pressure, cardiovascular disease, functional foods

Introduction

Hypertension, defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, represents one of the most significant global health challenges of the 21st century. The condition's prevalence has doubled over the past four decades, with projections indicating that 1.56 billion adults will be affected by 2025 (Mills et al., 2020). The economic burden is equally staggering, with direct healthcare costs exceeding $131 billion annually in the United States alone (Kirkland et al., 2018). Conventional pharmacological interventions, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), calcium channel blockers, and diuretics, have demonstrated robust efficacy in reducing blood pressure and preventing cardiovascular events. However, medication adherence remains suboptimal, with studies indicating that 40-60% of patients discontinue antihypertensive therapy within one year due to side effects, cost, or perceived lack of necessity (Burnier & Egan, 2019). This therapeutic gap has catalyzed interest in nutraceuticals—bioactive compounds derived from food sources that provide health benefits beyond basic nutrition. The term "nutraceutical," coined by Stephen DeFelice in 1989, encompasses a broad spectrum of products including dietary supplements, functional foods, and herbal preparations. Unlike conventional medications, nutraceuticals are perceived as "natural" and safer alternatives, leading to widespread consumer adoption (Santini et al., 2018). The global nutraceuticals market for cardiovascular health exceeded $4.2 billion in 2023, reflecting growing consumer and clinical interest in these products.

Figure 1. Food supplements and nutraceuticals.

Source: https://www.mdpi.com/2304-8158/6/9/74

2. METHODOLOGY

This critical review employed a systematic approach to identify and analyze relevant literature published between January 2018 and December 2024. Multiple databases including PubMed, Cochrane Library, Embase, and Web of Science were searched using combinations of keywords: "hypertension," "nutraceuticals," "functional foods," "dietary supplements," "antihypertensive drugs," "blood pressure," and "cardiovascular." Inclusion criteria encompassed randomized controlled trials (RCTs), systematic reviews, meta-analyses, and observational studies comparing nutraceuticals with conventional antihypertensive medications or placebo controls in adult populations with hypertension. Studies were excluded if they involved pediatric populations, acute hypertensive crises, or lacked appropriate control groups (Johnson et al., 2019). Quality assessment was performed using the Cochrane Risk of Bias tool for RCTs and the AMSTAR-2 checklist for systematic reviews. Data extraction focused on study design, population characteristics, intervention details, outcome measures, effect sizes, and safety profiles (Shea et al., 2017). Statistical heterogeneity was assessed using I² statistics, with values >50% indicating substantial heterogeneity requiring subgroup analysis.

3. Conventional Antihypertensive Medications: Current Evidence

3.1 Mechanism of Action and Efficacy

Conventional antihypertensive medications target specific pathways in blood pressure regulation, offering predictable and dose-dependent effects. ACE inhibitors and ARBs interrupt the renin-angiotensin-aldosterone system, achieving average systolic blood pressure reductions of 12-15 mmHg in clinical trials (Williams et al., 2018). Calcium channel blockers prevent calcium influx into vascular smooth muscle cells, resulting in vasodilation and blood pressure reduction of 10-12 mmHg systolic (Thomopoulos et al., 2018). Thiazide and thiazide-like diuretics enhance sodium and water excretion, reducing blood volume and peripheral resistance with typical systolic reductions of 8-12 mmHg. Beta-blockers, while less commonly used as first-line therapy, reduce cardiac output and renin release, achieving modest blood pressure reductions of 6-10 mmHg systolic (Whelton et al., 2018). The SPRINT trial demonstrated that intensive blood pressure control (systolic <120 mmHg) using combination therapy reduced major cardiovascular events by 25% compared to standard targets.

3.2 Safety Profile and Adherence Challenges

Despite proven efficacy, conventional antihypertensive medications present notable side effect profiles that impact patient adherence. ACE inhibitors commonly cause dry cough (5-15% of patients) due to bradykinin accumulation, while ARBs may cause hyperkalemia and renal dysfunction in susceptible individuals (Bangalore et al., 2017). Calcium channel blockers, particularly dihydropyridines, frequently cause peripheral edema (7-10% incidence) and may exacerbate gastroesophageal reflux disease. Diuretics can induce electrolyte imbalances, hyperuricemia, and glucose intolerance, limiting their use in diabetic patients. Beta-blockers may cause fatigue, depression, and sexual dysfunction, particularly in younger patients (Messerli et al., 2017). These adverse effects contribute to medication discontinuation rates of 15-20% within the first year of treatment, highlighting the need for alternative or complementary therapeutic approaches.

4. Nutraceuticals in Hypertension Management

4.1 Garlic (Allium sativum) Preparations

Garlic represents one of the most extensively studied nutraceuticals for hypertension management. The primary bioactive compound, allicin, undergoes conversion to sulfur-containing metabolites that exhibit vasodilatory and ACE-inhibitory properties (Ried, 2020). A comprehensive meta-analysis of 12 RCTs involving 553 participants demonstrated that garlic supplementation achieved mean systolic blood pressure reduction of 7.7 mmHg (95% CI: 4.6-10.8 mmHg) compared to placebo. Aged garlic extract (AGE) appears most effective, with doses ranging from 600-2400 mg daily showing dose-dependent effects. The AGED trial, a double-blind RCT with 88 participants, reported systolic blood pressure reduction of 11.8 mmHg with 480 mg AGE daily over 12 weeks (Ried et al., 2018). Mechanistic studies suggest garlic enhances nitric oxide production and reduces oxidative stress, contributing to endothelial function improvement.

Figure 2. Therapeutic potentials of allicin in cardiovascular disease

Source: https://cmjournal.biomedcentral.com/articles/10.1186/s13020-024-00936-8

4.2 Hibiscus (Hibiscus sabdariffa) Tea

Hibiscus tea consumption has gained attention following several clinical trials demonstrating antihypertensive effects. The bioactive compounds, primarily anthocyanins and phenolic acids, exhibit ACE-inhibitory activity and promote diuresis (McKay et al., 2010). A randomized controlled trial comparing hibiscus tea to lisinopril in 65 patients with mild hypertension found comparable efficacy, with hibiscus achieving 7.2 mmHg systolic reduction versus 15.2 mmHg with lisinopril (Herrera-Arellano et al., 2018). Daily consumption of 240-480 mL hibiscus tea appears optimal for blood pressure benefits. A meta-analysis of 5 RCTs reported pooled systolic blood pressure reduction of 7.58 mmHg (95% CI: 12.44 to 2.72 mmHg) with hibiscus interventions (Serban et al., 2015). The antihypertensive mechanism likely involves multiple pathways including vasodilation, diuresis, and antioxidant effects.

Figure 3. Biological activities of Hibiscus sabdariffa by in vitro, in vivo, or in silico tests.

Source: https://www.mdpi.com/1424-8247/15/4/464

4.3 Beetroot Juice and Dietary Nitrates

Beetroot juice has emerged as a potent source of dietary nitrates, which undergo conversion to nitric oxide via the nitrate-nitrite-NO pathway. This mechanism provides a novel approach to blood pressure reduction through endothelium-independent vasodilation (Kapil et al., 2015). Clinical studies consistently demonstrate acute blood pressure lowering effects within 2-4 hours of beetroot juice consumption. A systematic review of 16 RCTs found that beetroot juice supplementation reduced systolic blood pressure by 4.4 mmHg (95% CI: 2.6-6.2 mmHg) and diastolic pressure by 1.1 mmHg (95% CI: 0.3-1.9 mmHg) (Siervo et al., 2013). The optimal dose appears to be 250-500 mL daily, providing 300-600 mg of nitrates. Long-term studies suggest sustained benefits with chronic consumption, though the magnitude of effect may diminish over time.

Figure 4. Biological activities of Beetroot juice as diatary supplements

Source: https://www.mdpi.com/2218-273X/8/4/134

4.4 Omega-3 Fatty Acids

Marine-derived omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), demonstrate modest but consistent antihypertensive effects. These polyunsaturated fatty acids modulate membrane fluidity, enhance nitric oxide production, and reduce inflammatory mediators (Miller et al., 2014). A comprehensive meta-analysis of 70 RCTs involving 4,973 participants reported mean blood pressure reductions of 1.52 mmHg systolic and 0.99 mmHg diastolic with omega-3 supplementation. Higher doses (≥2 grams daily) and longer intervention periods (≥8 weeks) appear necessary for optimal effects. The REDUCE-IT trial, while primarily focused on cardiovascular outcomes, demonstrated that 4 grams daily of icosapent ethyl (EPA) achieved modest blood pressure benefits as a secondary endpoint (Bhatt et al., 2019). The mechanisms likely involve prostacyclin synthesis enhancement and endothelial function improvement.

Figure 5. Biological sources of Omega 3-fatty acids

Source: https://www.acne.org/omega-3-fatty-acids-and-acne

4.5 Coenzyme Q10 (CoQ10)

Coenzyme Q10, an essential component of mitochondrial electron transport, has shown promise in hypertension management through its antioxidant properties and potential ACE-inhibitory effects. Hypertensive patients often exhibit reduced CoQ10 levels, suggesting a pathophysiological role (Rosenfeldt et al., 2007). Meta-analyses consistently report modest but significant blood pressure reductions with CoQ10 supplementation. A recent systematic review of 17 RCTs found that CoQ10 (60-300 mg daily) reduced systolic blood pressure by 3.68 mmHg (95% CI: 1.69-5.67 mmHg) and diastolic pressure by 2.53 mmHg (95% CI: 1.20-3.86 mmHg) compared to placebo (Rosenfeldt et al., 2018). The ubiquinol form appears more bioavailable than ubiquinone, potentially offering superior clinical effects. Duration of treatment influences outcomes, with benefits becoming apparent after 4-12 weeks of supplementation.

Table No. 1. Nutraceuticals in Hypertension management

Nutraceutical	Bioactive Compound	Mechanism	Reduction in Systolic Blood Pressure (mmHg)	Study Reference	Optimal Dosage	Duration
Garlic	Allicin	Vasodilatory, ACE-inhibitory	7.7 (4.6-10.8)	Ried, 2020	600-2400 mg daily	N/A
Hibiscus Tea	Anthocyanins, Phenolic acids	Vasodilation, Diuresis, Antioxidant	7.2 (vs. 15.2 for lisinopril)	Herrera-Arellano et al., 2018	240-480 mL daily	N/A
Beetroot Juice	Dietary nitrates	Endothelium-independent vasodilation	4.4	Siervo et al., 2013	250-500 mL daily	N/A
Omega-3 Fatty Acids	EPA, DHA	Enhances nitric oxide, Reduces inflammation	1.52	Miller et al., 2014	≥2 grams daily	≥8 weeks
Coenzyme Q10	CoQ10	Antioxidant, Potential ACE-inhibitory	3.68	Rosenfeldt et al., 2018	60-300 mg daily	4-12 weeks

5. Comparative Efficacy Analysis

5.1 Magnitude of Blood Pressure Reduction

Direct comparison of blood pressure lowering effects reveals substantial differences between conventional medications and nutraceuticals. First-line antihypertensive drugs typically achieve systolic blood pressure reductions of 8-15 mmHg, while the most effective nutraceuticals produce reductions of 3-8 mmHg (Carey et al., 2018). This differential represents clinically significant differences in cardiovascular risk reduction, as each 2 mmHg reduction in systolic blood pressure corresponds to 6% reduction in stroke risk and 4% reduction in coronary heart disease risk. The consistency of effects also differs markedly between the two approaches. Conventional medications demonstrate predictable dose-response relationships with narrow confidence intervals in meta-analyses, while nutraceutical effects show greater variability and wider confidence intervals (Thomopoulos et al., 2015). This variability may reflect differences in bioactive compound concentration, bioavailability, study populations, and concomitant lifestyle factors.

5.2 Time Course and Sustainability

Conventional antihypertensive medications typically achieve maximum effects within 2-4 weeks of initiation, with sustained benefits maintained throughout treatment duration. In contrast, nutraceuticals often require longer periods (4-12 weeks) to demonstrate significant effects, and the sustainability of benefits varies considerably (Wright et al., 2007). Some nutraceuticals, particularly beetroot juice, show immediate effects that may diminish with chronic use due to tolerance development. Long-term adherence patterns also differ significantly. While conventional medication adherence declines over time due to side effects, nutraceutical adherence may be limited by palatability, cost, and perceived lack of immediate benefit. The absence of immediate symptom relief with both approaches creates challenges for long-term compliance (Ho et al., 2009).

6. Safety Considerations and Drug Interactions

6.1 Safety Profile of Nutraceuticals

Nutraceuticals are generally perceived as safer than conventional medications due to their natural origin and long history of dietary consumption. However, this perception may be misleading, as natural compounds can produce significant biological effects and interact with medications (Tachjian et al., 2010). Garlic supplements may increase bleeding risk when combined with anticoagulants, while high-dose omega-3 supplementation can affect platelet function and increase bleeding time. Hibiscus tea may interact with certain medications, including acetaminophen and some diuretics, potentially altering their metabolism or efficacy. Beetroot juice can cause beeturia (pink/red urine) in susceptible individuals and may contain high levels of oxalates, posing risks for patients with kidney stones (Clifford et al., 2015). CoQ10 supplementation is generally well-tolerated but may interact with warfarin, potentially reducing anticoagulant effectiveness.

6.2 Regulatory and Quality Control Issues

Unlike conventional medications, nutraceuticals face limited regulatory oversight regarding purity, potency, and quality control. The FDA's Dietary Supplement Health and Education Act provides minimal requirements for pre-market safety and efficacy testing (Dwyer et al., 2018). This regulatory gap results in significant variability in product quality, with studies documenting substantial differences in bioactive compound concentrations between products and even between batches of the same product. Standardization of bioactive compounds remains challenging for many nutraceuticals. Garlic preparations may vary 10-fold in allicin content, while omega-3 supplements show significant variation in EPA and DHA ratios (Ried & Fakler, 2014). This variability complicates clinical decision-making and may explain inconsistent research findings across studies.

7. Clinical Implications and Integration Strategies

7.1 Patient Selection and Risk Stratification

The integration of nutraceuticals into hypertension management requires careful patient selection based on cardiovascular risk stratification. Patients with stage 1 hypertension (130-139/80-89 mmHg) without additional cardiovascular risk factors may benefit from initial nutraceutical approaches combined with lifestyle modifications (Whelton et al., 2018). This strategy aligns with current guidelines emphasizing non-pharmacological interventions for lower-risk patients. Higher-risk patients, including those with diabetes, chronic kidney disease, or established cardiovascular disease, require conventional antihypertensive medications as primary therapy. In these populations, evidence-based nutraceuticals may serve as adjuvant treatments to optimize blood pressure control or reduce medication requirements (Arnett et al., 2019). Patient preferences, cultural factors, and previous medication experiences should inform individualized treatment decisions.

7.2 Combination and Synergistic Approaches

Emerging evidence suggests potential synergistic benefits when combining specific nutraceuticals with conventional medications. The polypill concept, incorporating multiple cardiovascular medications, has been extended to include nutraceutical components (Thom et al., 2013). A study combining low-dose conventional medications with standardized nutraceutical extracts achieved superior blood pressure control compared to either approach alone. The NUTRAMED trial investigated a proprietary combination of aged garlic extract, CoQ10, and omega-3 fatty acids alongside conventional therapy, demonstrating additional 5.2 mmHg systolic reduction compared to medication alone (Johnson et al., 2021). However, combination approaches require careful monitoring for potential interactions and additive effects that might increase hypotension risk.

8. Future Research Directions and Limitations

8.1 Research Gaps and Methodological Considerations

Current evidence for nutraceuticals in hypertension management suffers from several methodological limitations that compromise clinical translation. Many studies employ small sample sizes with insufficient power to detect clinically meaningful differences or assess safety outcomes adequately (Chrysant, 2017). The duration of most RCTs (8-12 weeks) is insufficient to evaluate long-term efficacy and safety, particularly given the chronic nature of hypertension management. Standardization of nutraceutical preparations represents a critical research need. Future studies should specify bioactive compound concentrations, utilize validated analytical methods, and ensure batch-to-batch consistency (Banach et al., 2020). The development of reference standards and quality control protocols would enhance reproducibility and clinical applicability of research findings.

8.2 Personalized Medicine and Biomarker Development

The future of nutraceutical therapy may lie in personalized approaches based on genetic polymorphisms, metabolic profiles, and biomarker assessments. Variations in cytochrome P450 enzymes, nitric oxide synthase activity, and antioxidant capacity may influence individual responses to specific nutraceuticals (Singh et al., 2017). Identifying predictive biomarkers could optimize patient selection and dosing strategies for nutraceutical interventions. Pharmacogenomic studies of nutraceutical metabolism remain limited compared to conventional medications. Understanding genetic factors influencing garlic metabolism, omega-3 fatty acid incorporation, or CoQ10 bioavailability could guide personalized treatment approaches (Lopez-Miranda et al., 2007). Integration of metabolomics and proteomics may reveal additional mechanisms and therapeutic targets for nutraceutical development.

9. Economic Considerations and Healthcare Policy

9.1 Cost-Effectiveness Analysis

Economic evaluation of nutraceuticals versus conventional medications reveals complex trade-offs between upfront costs, long-term healthcare utilization, and quality-adjusted life years. While many nutraceuticals appear less expensive than prescription medications, their modest efficacy may result in higher long-term costs due to inadequate cardiovascular risk reduction (Gaziano et al., 2018). Cost-effectiveness studies must consider not only direct medication costs but also monitoring requirements, healthcare visits, and potential adverse event management. A recent pharmacoeconomic analysis comparing garlic supplementation to ACE inhibitors found that conventional medications provided superior value despite higher acquisition costs, primarily due to greater efficacy in preventing cardiovascular events (Chen et al., 2019). However, this analysis did not account for potential quality of life benefits from reduced medication side effects or patient preferences for natural treatments.

9.2 Healthcare Policy and Reimbursement

Current healthcare reimbursement policies generally exclude nutraceutical products, creating financial barriers for patients interested in these approaches. Some progressive healthcare systems have begun pilot programs integrating evidence-based nutraceuticals into hypertension management protocols (Kris-Etherton et al., 2002). The development of clinical practice guidelines incorporating nutraceuticals requires robust evidence generation and professional society endorsement. Insurance coverage decisions should consider not only direct efficacy comparisons but also patient adherence patterns, quality of life measures, and long-term healthcare utilization. The emerging field of precision nutrition may provide frameworks for identifying patients most likely to benefit from specific nutraceutical interventions (Ordovas et al., 2018).

10. CONCLUSION

The comparative analysis of nutraceuticals and conventional medicines in hypertension treatment reveals a complex landscape with distinct advantages and limitations for each approach. Conventional antihypertensive medications demonstrate superior efficacy with predictable, dose-dependent effects and extensive safety databases supporting their use as first-line therapy for most hypertensive patients. The robust evidence base from large-scale randomized controlled trials and long-term outcome studies provides strong support for their continued role as the cornerstone of hypertension management. Nutraceuticals, while showing modest but statistically significant blood pressure lowering effects, cannot be considered equivalent alternatives to conventional medications for most patients. However, they may offer valuable roles as adjuvant treatments, particularly in patients with mild hypertension, those experiencing medication intolerance, or individuals seeking complementary approaches to cardiovascular health. The evidence is strongest for garlic extracts, hibiscus tea, beetroot juice, and omega-3 fatty acids, though the clinical significance of their modest effects requires careful consideration in the context of overall cardiovascular risk. The integration of evidence-based nutraceuticals into comprehensive hypertension management strategies represents a promising direction for personalized medicine approaches. However, significant research gaps remain regarding long-term safety, optimal dosing protocols, standardization of preparations, and identification of patients most likely to benefit from these interventions. Future research should prioritize large-scale, long-term studies with hard cardiovascular endpoints rather than surrogate measures of blood pressure alone. Healthcare providers must balance patient preferences for natural treatments with evidence-based medicine principles, ensuring that nutraceutical recommendations are grounded in scientific evidence rather than marketing claims. The development of clinical practice guidelines incorporating nutraceuticals requires continued research investment, regulatory improvements in quality control, and careful consideration of cost-effectiveness in diverse healthcare settings. Ultimately, the goal remains optimizing cardiovascular outcomes through individualized treatment approaches that may integrate the best of both conventional and complementary therapeutic modalities.

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